Mast Cell Regulation of Human Endometrial Matrix Metalloproteinases: A Mechanism Underlying Menstruation1

Abstract

Endometrial matrix metalloproteinases (MMPs), which increase dramatically at menstruation, are purported to cause the focal tissue breakdown at menstruation, but how their expression or activation is locally regulated is unknown. Mast cell activation occurs within perimenstrual endometrium, and we postulated that mast cell products would regulate endometrial MMPs. We have examined the interaction between human mast cells and endometrial stromal cells with regard to MMP production and activation. The human mast cell line (HMC-1) in coculture with stromal cells stimulated stromal cell proMMP-1 and proMMP-3, and to a lesser extent proMMP-2 production, with increasing stimulation as mast cell number increased. Mast cell-conditioned medium also increased both protein and mRNA for stromal proMMP-1 and proMMP-3, this being abrogated by preadsorption of mast cell-conditioned medium with antisera to interleukin-1 and tumor necrosis factor alpha. Mast cell-conditioned medium added to stromal cell culture medium in vitro along with added heparin (which stabilizes tryptase activity) resulted in the appearance of molecular weight forms indicative of active MMP-3 and MMP-1. Thus activated mast cells within the endometrium prior to menstruation have the potential to stimulate MMP production by endometrial stromal cells and to initiate precursor activation, and are likely to account for the local nature of endometrial MMP action resulting in foci of tissue breakdown at menstruation.

Mast Cell-Fibroblast Interactions Induce Matrix Metalloproteinase-9 Release from Fibroblasts: Role for IgE-Mediated Mast Cell Activation

“…However, the physiological stimuli that induce MMP-9 production during inflammatory conditions and the role of particular cells in MMP-9 production in the lung are not fully understood. Mast cells, and in particular tryptase and TNF released from mast cells, have been implicated in the up-regulation of MMP in human aortic endarterectomy specimens (42) and in endometrial stroma cells (43), but there is no available information about the direct role of mast cells in MMP-9 release in lung or airway inflammatory conditions. Our results indicate that direct adhesive interactions between mast cells and fibroblasts, as well as mast cell mediators such as TNF, may be important for release of MMP-9 in airway inflammatory conditions.…”

Mast cells degranulation affects angiogenesis in the rat uterine cervix during pregnancy

“…However, during angiogenesis, local and controlled degradation of connective tissue is essential for neovascular sprouting and elongation (Kahari & SaarialhoKere 1997). Mast cells could mediate this process since it has been demonstrated that activated MCs have the potential to stimulate the production of matrix metalloproteinases (MMPs) by endometrial stromal cells and to set up a cascade of MMP activation within the endometrium (Zhang et al 1998). It has been demonstrated that histamine and heparin have potent angiogenic effects.…”

Inflammatory pathways in female reproductive health and disease

“…Mast cell activation results in the release of potent regulators such as TNF, histamine and mast cell-specific proteases preceding menstruation (Sivridis et al 2001). The importance of such cellular interactions has been demonstrated by the production and activation of MMP1 and MMP3 by endometrial stromal cells during co-culture with mast cells (Zhang et al 1998).…”